Low Doses of Non-NMDA Glutamate Receptor Agonists Alter Neurobehavioural Development in the Rat

While it is known that glutamate is critical to CNS development and function, less is known about the role of kainate receptors, a subclass of ionotropic glutamate receptors, during ontogeny. This is especially true with respect to the emergence and expression of behaviour. It is also known that the neonatal CNS differs from that of adults with respect to excitatory amino acid (EAA) toxicity. Our aim was to determine the effects of early low-dose stimulation of kainate receptors on physical and behavioural development in the rat. Saline, one of two subtoxic doses of domoic acid (DOM) (5 and 20 microg/kg), or in a parallel study, saline, or one of two pharmacologically equivalent doses of kainic acid (KA) (25 and 100 microg/kg), were systemically administered once daily from postnatal days (PNDs) 8-14. While DOM or KA had no effect on typical measures of toxicity such as weight gain, acoustic startle, ultrasonic vocalizations (UVs), or maternal retrieval, these doses were shown to be physiologically relevant, producing particular group differences in eye opening, conditioned place preference, and activity levels. We conclude that administration of very low doses of selective kainate receptor agonists during the second postnatal week produces changes in neurobehavioural development in the rat.